title: Potential function of granulysin, other related effector molecules and lymphocyte subsets in patients with TB and HIV/TB coinfection.
abstract: BACKGROUND
  Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy.
  
  
  OBJECTIVE
  To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9(+)Vδ2(+) T cells, CD4(+) T cells and CD8(+) T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection.
  
  
  METHODS
  Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry.
  
  
  RESULTS
  Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8(+) T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed.
  
  
  CONCLUSIONS
  The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Nada
authors.initials: N
authors.lastname: Pitabut
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Sakurada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Chutharut
authors.initials: C
authors.lastname: Ridruechai
authors.forename: Junko
authors.initials: J
authors.lastname: Tanuma
authors.forename: Takahiro
authors.initials: T
authors.lastname: Aoki
authors.forename: Pacharee
authors.initials: P
authors.lastname: Kantipong
authors.forename: Surachai
authors.initials: S
authors.lastname: Piyaworawong
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Panadda
authors.initials: P
authors.lastname: Dhepakson
authors.forename: Hideki
authors.initials: H
authors.lastname: Yanai
authors.forename: Norio
authors.initials: N
authors.lastname: Yamada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Masaji
authors.initials: M
authors.lastname: Okada
authors.forename: Srisin
authors.initials: S
authors.lastname: Khusmith
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000150:complications* / Q000503:physiopathology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human
keywords: Granulysin; HIV; HIV/TB Coinfection; Lymphocytes Subsets.; TB